POS0739 THE RENAL ACTIVITY INDEX FOR LUPUS (RAIL) DIFFERENTIATES ACTIVE AND INACTIVE NEPHRITIS IN ADULT PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)
Authors: E. Cody, H. Brunner, B. Huang, T. Qiu, P. Devarajan, M. Ramaswamy, D. Sinibaldi, P. Z. Brohawn, J. Knagenhjelm, F. Jones, R. Tummala, C. Lindholm, W. White
Journal: Annals of the Rheumatic Diseases (2022)

Background Lupus nephritis (LN) confers a poor prognosis, with lack of effective laboratory tests to diagnose and evaluate therapies. We have demonstrated that the RAIL score, based on a set of six urinary biomarkers ( NGAL, KIM-1, MCP-1, adiponectin, hemopexin, ceruloplasmin) is sensitive and specific in adult patients with active LN, using renal biopsy as reference. 1,2 RAIL has been shown in the pediatric population to be effective in distinguishing inactive vs active LN with no effect from mycophenolate mofetil (MMF) treatment. A comparable study has not been conducted in an adult population. Objectives To assess the ability of RAIL to discriminate patients with active LN vs active non-renal SLE and to evaluate if RAIL performance varies by MMF treatment using urine samples from adult LN patients. Methods Urine samples were obtained at baseline in two clinical trials: a phase 2 study in adult patients with biopsy-proven active Class III and IV LN ( NCT02547922 ) and a subset of patients from the phase 3 trial in adults with active non-renal SLE ( NCT02446912 ) who had baseline renal BILAG scores C, D, or E. RAIL biomarkers were assayed using single-plex assays. Patient demographics and clinical characteristics were compared between studies. Wilcoxon rank sum test was performed comparing the urinary biomarkers between the two studies and RAIL score was then calculated. Receiver operating characteristic (ROC) analyses were conducted assessing the ability for RAIL scores to distinguish patients with renal activity and involvement. Results Comparison of the patient demographic, clinical characteristics, and biomarkers is in the Table 1. Wilcoxon rank sum test showed the six urinary biomarkers were significantly different between two groups of patients as demonstrated (Table 1). Each of the RAIL biomarker concentrations and the creatinine-adjusted median score were higher in the active LN group than the SLE group ( P &lt;0.001). ROC analyses including RAIL score showed an area under the ROC curve of 0.8 (Figure 1), with odds ratio of log-transformed RAIL 2.027 (95% CI [1.587, 2.589]). There were no significant interactions between RAIL and MMF. RAIL remained significant after adjusting for estimated glomerular filtration rate (eGFR), which was not statistically significant. Table 1. Study Demographics and Biomarkers Variables LN study (N=131) SLE study (N=59) Observed N Observed Median (IQR) or % Observed N Observed Median (IQR) or % Demographics Age 131 34 (25, 42) 59 36 (28, 44) Sex, Female 109 83.21% 55 93.22% Race, White 56 42.75% 45 76.27% Ethnicity, Hispanic or Latino 61 46.56% 9 15.25% OCS use, yes 127 97.69% 57 96.61% MMF use, yes 95 72.52% 21 35.59% Spot UPCR (mg/mg) 128 2.13 (1.22, 4.04) 59 1.11 (0.55, 2.61) eGFR 130 91.8 (63.1, 125) 59 98.06 (81.91, 116.54) Non-renal SLEDAI-2K score 130 4 (4, 6) 59 12 (9, 13) Renal SLEDAI-2K score 130 4 (4, 8) 59 0 (0, 0) Biomarkers NGAL (ng/mL) 128 33.33 (17.55, 56.7) 58 19.47 (11.37, 42.05) MCP-1 (pg/mL) 128 658.24 (271.58, 1049.95) 58 275.62 (106.09, 481.99) Ceruloplasmin (ng/mL) 128 93.55 (44.5, 311.25) 58 47.2 (13.05, 231.25) Adiponectin (ng/mL) 128 42.45 (16.71, 139.64) 58 9.33 (3.35, 25.51) Hemopexin (ng/mL) 128 1876.8 (745.07, 4743.4) 58 513.4 (236.36, 1388.74) KIM-1 (pg/mL) 128 1673.5 (772.5, 2767) 58 864 (394, 1480) Creatinine (mg/mL) 128 0.7 (0.46, 1.3) 58 0.99 (0.46, 1.74) Adult RAIL score (creatinine adjusted ) 128 5.59 (4.31, 6.47 ) 58 3.57 (2.78, 4.47 ) eGFR, estimated glomerular filtration rate; IQR, interquartile range; KIM, kidney injury molecule; LN, lupus nephritis; MCP, monocyte chemotactic protein; MMF, mycophenolate mofetil; NGAL, neutrophil gelatinase-associated lipocalin; OCS, oral corticosteroid; SLEDAI-2K, SLE Disease Activity Index 2000; UPCR, urine protein/creatinine ratio. Conclusion The analyses performed suggest that creatinine-corrected RAIL discriminates between active LN and non-renal adult SLE, with RAIL scores not influenced by MMF use. References [1]Brunner HI. Arthritis Care Res (Hoboken ). 2016;68:1003–11. [2]Gulati G. Lupus . 2017;26:927–36. Acknowledgements Writing assistance by Kelly M. Hunter, PhD (Fishawack). This study was sponsored by AstraZeneca. Disclosure of Interests Ellen Cody: None declared, Hermine Brunner Speakers bureau: Novartis, Pfizer, GSK, Consultant of: AbbVie, Astra Zeneca-Medimmune, Biogen, Boehringer, Bristol Myers Squibb, Celgene, Lilly,EMD Serono, Idorsia, Cerocor, Janssen, GSK, F. Hoffmann-La Roche, Merck, Novartis, R-Pharm, Sanofi, Grant/research support from: Pfizer, Bin Huang: None declared, Tingting Qiu: None declared, Prasad Devarajan Speakers bureau: Reata, Alnylam, Dicerna, Consultant of: BioPorto Inc, Madhu Ramaswamy Shareholder of: AstraZeneca, Employee of: AstraZeneca, Dominic Sinibaldi Shareholder of: AstraZeneca, Employee of: AstraZeneca, Philip Z Brohawn Shareholder of: AstraZeneca, Employee of: AstraZeneca, Jacob Knagenhjelm Shareholder of: AstraZeneca, Employee of: AstraZeneca, Frederick Jones Shareholder of: AstraZeneca, Employee of: AstraZeneca, Raj Tummala Shareholder of: AstraZeneca, Employee of: AstraZeneca, Catharina Lindholm Employee of: AstraZeneca, Wendy White Shareholder of: AstraZeneca, Employee of: AstraZeneca